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Genetik der Epilepsien

Genetics of epilepsy

  • Leitthema
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Zusammenfassung

Etwa 3% aller Menschen erkranken an Epilepsie. Ungefähr 40% der Erkrankungen manifestieren sich im Kindesalter, und rund die Hälfte ist genetischen Ursprungs. Über 280 monogen vererbte Krankheitsbilder gehen fakultativ mit Epilepsie einher. Neben Stoffwechselstörungen und Hirnfehlbildungen gehören hierzu auch einige epileptische Enzephalopathien. Rund 98–99% der häufigen idiopathischen Epilepsien folgen allerdings einem polygenen Erbgang. Nur in wenigen Fällen konnten bisher Ionenkanaldefekte als Ursache identifiziert werden. Kürzlich wurde jedoch gezeigt, dass etwa 3% der Patienten mit idiopathischen Epilepsien kleine genomische Deletionen repetitiver DNA-Sequenzen (so genannte CNV, „copy number variants“) aufweisen. Einige dieser DNA-Abschnitte enthalten Ionenkanalgene oder Gene, die anderweitig an der Pathogenese von Epilepsien beteiligt sind. Für die Diagnosestellung oder die Abschätzung eines Epilepsierisikos können diese Befunde aber noch nicht verwendet werden. Durch neue Methoden der automatisierten Molekulargenetik wird die Zahl pathologischer genetischer Befunde innerhalb der nächsten Jahre exponentiell ansteigen.

Abstract

More than 3% of people will develop epilepsy during their lifetime (at least 2 unprovoked seizures within 2 years) with approximately 40% manifesting during childhood and 50% of genetic origin. More than 280 single gene diseases may be associated with epilepsy. Besides metabolic disorders and malformations involving the CNS, many types of epileptic encephalopathy belong to this group. However, 98–99% of common idiopathic epilepsies follow a complex (polygenic) mode of inheritance. Ion channels defects have been identified as the cause only in selected families and isolated cases. Recently, it could be shown that about 3% of individuals with idiopathic epilepsy carry genomic copy number variants (CNV), mostly deletions, containing 1–10 genes. Some of these DNA segments contain ion channel genes or genes required for CNS development. However, these findings are not useful for genetic counseling. Current methods of molecular biology (e.g exome sequencing) have already started to open a new area in the field of epilepsy genetics.

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Literatur

  1. Berg AT, Berkovic SF, Brodie MJ et al (2010) Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia 51:676–685

    Article  PubMed  Google Scholar 

  2. Berkovic SF, Howell RA, Hay DA, Hopper JL (1998) Epilepsies in twins: genetics of the major epilepsy syndromes. Ann Neurol 43:435–445

    Article  PubMed  CAS  Google Scholar 

  3. Combi R, Dalprà L, Ferini-Strambi L, Tenchini ML (2005) Frontal lobe epilepsy and mutations of the corticotropin-releasing hormone gene. Ann Neurol 58:899–904

    Article  PubMed  CAS  Google Scholar 

  4. Depienne C, Bouteiller D, Keren B et al (2009) Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females. PLoS Genet 5:e1000381

    Article  PubMed  Google Scholar 

  5. Doose H, Lunau H, Castiglione E, Waltz S (1998) Severe idiopathic generalized epilepsy of infancy with generalized tonic-clonic seizures. Neuropediatrics 29(5):229–238

    Article  PubMed  CAS  Google Scholar 

  6. Ebach K, Joos H, Doose H et al (2005) SCN1A mutation analysis in myoclonic astatic epilepsy and severe idiopathic generalized epilepsy of infancy with generalized tonic-clonic seizures. Neuropediatrics 36:210–213

    Article  PubMed  CAS  Google Scholar 

  7. Grosso S, Orrico A, Galli L et al (2007) SCN1A mutation associated with atypical Panayiotopoulos syndrome. Neurology 69:609–611

    Article  PubMed  CAS  Google Scholar 

  8. Hahn A, Neubauer BA (2009) Sodium and potassium channel dysfunctions in rare and common idiopathic epilepsy syndromes. Brain Dev 31:515–520

    Article  PubMed  Google Scholar 

  9. Harkin LA, McMahon JM, Iona X et al (2007) The spectrum of SCN1A-related infantile epileptic encephalopathies. Brain 130:843–852

    Article  PubMed  Google Scholar 

  10. Liao Y, Deprez L, Maljevic S et al (2010) Molecular correlates of age-dependent seizures in an inherited neonatal-infantile epilepsy. Brain 133:1403–1414

    Article  PubMed  Google Scholar 

  11. Mantegazza M, Gambardella A, Rusconi R et al (2005) Identification of an Nav1.1 sodium channel (SCN1A) loss-of-function mutation associated with familial simple febrile seizures. Proc Natl Acad Sci USA 102:18177–18882

    Article  PubMed  CAS  Google Scholar 

  12. Maljevic S, Wuttke TV, Lerche H (2008) Nervous system KV7 disorders: breakdown of a subthreshold brake. J Physiol 586:1791–1801

    Article  PubMed  CAS  Google Scholar 

  13. Mefford HC, Muhle H, Ostertag P et al (2010) Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies. PLoS Genet 20:e1000962

    Article  Google Scholar 

  14. Neubauer BA, Waldegger S, Heinzinger J et al (2008) KCNQ2 and KCNQ3 mutations contribute to different idiopathic epilepsy syndromes. Neurology 71:177–1783

    Article  PubMed  CAS  Google Scholar 

  15. Rosanoff MJ, Ottman R (2008) Penetrance of LGI1 mutations in autosomal dominant partial epilepsy with auditory features. Neurology 71:567–571

    Article  PubMed  Google Scholar 

  16. Scheffer IE, Turner SJ, Dibbens LM et al (2008) Epilepsy and mental retardation limited to females: an under-recognized disorder. Brain 131:918–922

    Article  PubMed  Google Scholar 

  17. Sisodiya SM, Mefford HC (2011) Genetic contribution to common epilepsies. Curr Opin Neurol 24:140–145

    Article  PubMed  Google Scholar 

  18. Steinlein OK, Bertrand D (2010) Nicotinic receptor channelopathies and epilepsy. Pflugers Arch 460:495–503

    Article  PubMed  CAS  Google Scholar 

  19. Stogmann E, Lichtner P, Baumgartner C et al (2006) Idiopathic generalized epilepsy phenotypes associated with different EFHC1 mutations. Neurology 67:2029–2031

    Article  PubMed  CAS  Google Scholar 

  20. Suls A, Mullen SA, Weber YG et al (2009) Early-onset absence epilepsy caused by mutations in the glucose transporter GLUT1. Ann Neurol 66:415–419

    Article  PubMed  CAS  Google Scholar 

  21. Suzuki T, Miyamoto H, Nakahari T (2009) Efhc1 deficiency causes spontaneous myoclonus and increased seizure susceptibility. Hum Mol Genet 18:1099–1109

    Article  PubMed  CAS  Google Scholar 

  22. Weber YG, Jacob M, Weber G, Lerche H (2008) A BFIS-like syndrome with late onset and febrile seizures: suggestive linkage to chromosome 16p11.2–16q12.1. Epilepsia 49:1959–1964

    Article  PubMed  Google Scholar 

  23. Yamada K, Miura K, Hara K et al (2010) A wide spectrum of clinical and brain MRI findings in patients with SLC19A3 mutations. BMC Med Genet 11:171

    Article  PubMed  CAS  Google Scholar 

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  1. Abteilung für Neuropädiatrie, Sozialpädiatrie und Epileptologie, Zentrum Kinderheilkunde und Jugendmedizin, Universitätsklinikum Gießen und Marburg, Feulgenstraße 12, 35385, Gießen, Deutschland

    B.A. Neubauer & A. Hahn

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  1. B.A. Neubauer
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  2. A. Hahn
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Correspondence to B.A. Neubauer.

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Neubauer, B., Hahn, A. Genetik der Epilepsien. Monatsschr Kinderheilkd 159, 714–720 (2011). https://doi.org/10.1007/s00112-011-2395-5

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  • DOI: https://doi.org/10.1007/s00112-011-2395-5

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